Direct Arylation via C–H Activation - New Trends in Cross-Coupling: Theory and Applications - page 556

H

Pd (OAc) 2 (0.1-2.0 mol%)
ligand E
K 2 CO 3 ,DMA,Ag 2 CO 3
130 °C

I

R 2

R 1

O

R 1

R 2

O

Scheme 12.7 Effect of silver salt in Pd-catalyzed intramolecular direct arylation.

H

X

O

L n Pd(0)

O

L n

K

X
I

L n

Pd II

H

Pd II X KI

O

H

O

O

catalyst deactivation
through palladate formation

K 2 CO 3

KHCO 3 +KI

HI

Figure 12.3 Proposed mechanism for Pd-catalyzed intramolecular arylation.

H

X

R 2

R 1

Pd (OH) 2 /carbon (10 mol% Pd)
KOAc, DMA, 130 °C

O

R 1

R 2

O

X=Br,I

Scheme 12.8 Application of Pearlman's catalyst for direct arylation.

Br H

Pd (OAc) 2 (10 mol%)
ligand

Cl

(20 mol%)
KOAc, DMA, 130 °C
olefin (1 equiv)

D

R

Y

X

X Y

X-Y = O-CH 2 , Piv-N-CH 2 ,Ms-N-CH 2 ,NH

R=Ph,CO 2 t Bu

Scheme 12.9 Tandem-sequential Heck-direct arylation.

species was further confirmed by the observation that no product was
formed in the presence of solid-phase thiol scavenger resin.
Further study revealed that these methods can be applied to tandem
Heck-direct arylation reaction sequences. 27 Substrates containing both
bromide and chloride functional groups were reacted with a Heck acceptor
(Scheme 12.9). An interesting tandem-sequential Heck-direct arylation-
hydrogenation was observed on replacing the nitrogen atmosphere of the
completed reaction with hydrogen (Scheme 12.10).
To gain an insight into the mechanism of Pd-catalyzed direct arylation
reactions, Fagnou and co-workers conducted a series of experiments. 22
Competition experiments established a slight preference for electron-rich
arenes. Direct arylation with a simple aryl bromide resulted in a primary